Coxiella burnetii Infection Increases Transferrin Receptors on J774A.1 Cells

Inoculation with viable, but not inactivated, Coxiella burnetii resulted in the increased expression of transferrin receptors (TfR) in the murine macrophage-like cell line J774A.1. This upregulation was evident in immunoblots as early as 6 h postinfection, with TfR levels continuing to increase through the first 24 h of infection. Fluorescent labeling revealed that TfR upregulation occurred throughout infected monolayers, eliminating the possibility that it reflected a response by a minor subset of host cells. In addition, TfR trafficking did not appear to be affected by C. burnetii infection. Consistent with the increase in TfRs, inoculation with viable C. burnetii resulted in a 2.5-fold increase in total cellular iron by 12 h postinoculation. Our further findings that the chelation of intracellular iron arrests C. burnetii replication and that C. burnetii metabolic activities in vitro are affected by iron concentration suggest that TfR upregulation is a salient factor in C. burnetii infection, and we speculate that it may represent a significant virulence mechanism.